Active Systemic Lupus Erythematosus
Conditions
Keywords
Active Systemic Lupus Erythematosus
Brief summary
The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in adult participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).
Detailed description
This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. Participants must be taking either 1 or any combination of the following: oral corticosteroids (OCS), antimalarial, and/or immunosuppressants. The study will be performed in adult participants aged 18 to 70 years of age. Approximately 360 participants receiving SOC treatment will be randomised in a 1:1 ratio to receive a fixed intravenous dose of anifrolumab 300 mg or placebo every 4 weeks for a total of 13 doses (Week 0 to Week 48), with the primary endpoint evaluated at the Week 52 visit. Investigational product will be administered as an intravenous infusion (IV) via an infusion pump over a minimum of 30 minutes, every 4 weeks.
Interventions
BIOLOGICALAnifrolumab
Intravenous infusion (IV)
DRUGPlacebo
Intravenous infusion (IV)
Sponsors
PRA Health Sciences
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 through 70 years at the time of screening 2. Diagnosis of paediatric or adult SLE with a diagnosis of SLE according to the ACR 1982 revised criteria ≥24 weeks prior to signing the Informed Consent form (ICF) 3. Currently receiving at least 1 of the following: 1. Where prednisone is the single standard of care medication (ie, the subject is not concurrently receiving any medication listed in inclusion criterion 3(c)), a dose of oral prednisone ≥7.5 mg/day but ≤40 mg/day (or prednisone equivalent) for a minimum of 8 weeks prior to Day 1. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation 2. Where prednisone is not the single standard of care medication (ie, the subject is concurrently receiving at least one medication listed in inclusion criterion 3(c), a dose of oral prednisone (≤40 mg/day) (or prednisone equivalent) for a minimum of 2 weeks prior to signing of the ICF. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation. 3. Any of the following medications administered for a minimum of 12 weeks prior to signing the informed consent, and at a stable dose for a minimum of 8 weeks prior to signing the informed consent and through Day 1: (i) Azathioprine ≤200 mg/day (ii) Antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150 mg/day 4. Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at least 1 of which must be: 1. Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay (IFA) at the central laboratory with titre ≥1:80; OR 2. Anti-dsDNA antibodies at screening elevated to above normal (including indeterminate), as per the central laboratory; OR 3. Anti-Smith (anti-Sm) antibody at screening elevated to above normal as per the central laboratory 5. At Screening, Disease Activity Adjudication Group confirmation of: SLEDAI-2K Criteria: SLEDAI-2K score ≥6 points and Clinical SLEDAI-2K score ≥4 points. The Clinical SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures. 6. Must not have active or latent TB on either chest radiograph or by quantiferon gold test 7. Day 1 Clinical SLEDAI-2K score ≥4 points 8. OCS dose stable for at least 2 weeks prior to randomisation 9. Stable SLE SOC treatment at the time of randomisation 10. Women of child-bearing potential must have a negative serum β-hCG test at and negative urine pregnancy test at randomisation prior to administration of investigational product
Exclusion criteria
1. Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater 2. Receipt of any of the following: (a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1 3. History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome. 4. Active severe or unstable neuropsychiatric SLE 5. Active severe SLE-driven renal disease 6. Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE or SSc. 7. History of, or current, inflammatory joint or skin disease other than SLE 8. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the ICF 9. 26.27. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation 10. Confirmed positive test for hepatitis B or hepatitis C 11. Any severe herpes infection at any time prior to Week 0 (Day 1) 12. Opportunistic infection requiring hospitalisation or intravenous antimicrobial treatment within 3 years prior to randomization 13. History of cancer, apart from: 1. Squamous or basal cell carcinoma of the skin that has been successfully treated 2. Cervical cancer in situ that has been successfully treated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 | Baseline; Week 52 | Composite endpoint BICLA was defined by meeting all of the following criteria: * Reduction of all baseline British Isles Lupus Assessment Group (BILAG)-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B * No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of \>0 points in SLEDAI-2K * No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved and Maintained an Oral Corticosteroids (OCS) Dose of ≤7.5 mg/Day at Week 52 in the Sub-Group of Participants With Baseline OCS ≥10 mg/Day | Week 40; Week 52 | Maintained OCS reduction was defined by meeting all of the following criteria: * Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 * Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment |
| Number of Participants With a ≥50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12 in The Sub-Group of Participants With Baseline CLASI Activity Score of ≥10 | Baseline; Week 12 | 50% reduction in CLASI activity score compared to baseline was defined by meeting all of the following criteria: * Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment |
| Number of Participants With ≥50% Reduction in Joint Counts at Week 52 in The Sub-group of Participants With ≥6 Swollen and ≥6 Tender Joints at Baseline | Baseline; Week 52 | 50% reduction in the number of swollen and tender joints compared to baseline was defined by meeting all of the following criteria: * Achieve ≥50% reduction from baseline in the number of swollen and tender joints, separately * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment |
| Annualised Flare Rate Through 52 Weeks | Baseline to Week 52 | A flare was defined as either 1 or more new British Isle Lupus Assessment Group (BILAG-2004) A or 2 or more new BILAG-2004 B items compared to the previous visit. The occurrence of a new flare was checked for each available visit versus the previous available visit up to Week 52. If no new flares occurred, the number of flares was set to 0. Otherwise all flares were counted leading to the maximum number of flares of 13. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25 (1 year). The flare exposure time is the time up to Week 52 (date of BILAG-2004 assessment at Week 52) or up to the date of last available BILAG-2004 assessment. |
| Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 in the IFN Test-High Sub-group | Baseline; Week 52 | Defined by meeting all of the following criteria: * Reduction of all baseline British Isles Lupus Assessment Group (BILAG)-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B * No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline to \>0 points in SLEDAI-2K * No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment |
| Number of Participants With One or More Adverse Events of Special Interest (AESIs) | Baseline to end of study (Maximum of 60 weeks) | An AESI is an adverse event (AE) of scientific and medical concern specific to understanding biologics. An AESI may be serious or non-serious. AESI are serious infections, including non-opportunistic serious infections, opportunistic infections, anaphylaxis, malignancy, herpes zoster, tuberculosis (TB) (including latent TB), influenza, vasculitis (non-systemic lupus erythematosus \[SLE\]), and major adverse cardiovascular events (MACE) (including stroke, myocardial infarction \[MI\], or cardiovascular death). AESIs were collected throughout the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE). |
| Number of Participants With a Potentially Clinically Important Change From Baseline in Vital Sign Measurements | Baseline to end of study (Maximum of 60 weeks) | Vital sign measurements included oral temperature, blood pressure (BP), pulse rate, and respiratory rate. Vital signs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE). |
| Number of Participants With a Potentially Clinically Important Change From Baseline in Clinical Laboratory Tests | Baseline to end of study (Maximum of 60 weeks) | Clinical laboratory tests were analyzed in a central clinical laboratory and included hematology, serum chemistry and urinalysis tests. Laboratory values were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE). |
| Number of Participants With One or More Adverse Events (AEs) | Baseline to end of study (Maximum of 60 weeks) | An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE). The reported value is inclusive of serious and non-serious AEs. |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, France, Germany, Japan, Lithuania, Mexico, Russia, South Africa, South Korea, Spain, United States
Participant flow
Recruitment details
Participants took part in the trial at 119 sites in 15 countries worldwide.
Pre-assignment details
8 participants were assigned study drug, but due to non-compliance were analyzed separately (not included in the participant flow). 3 additional participants were assigned study drug & included in the participant flow, but did not receive study drug due to an adverse event (1 Anifrolumab 300mg) & failure to meet randomization criteria (2 Placebo).
Participants by arm
| Arm | Count |
|---|---|
| Anifrolumab 300 mg Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses). | 180 |
| Placebo Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses). | 182 |
| Total | 362 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 7 |
| Overall Study | Condition Under Investigation Worsened | 1 | 4 |
| Overall Study | Failure to Meet Randomization Criteria | 0 | 2 |
| Overall Study | Lack of Efficacy | 2 | 8 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Miscellaneous | 5 | 4 |
| Overall Study | Severe Non-Compliance to Protocol | 0 | 1 |
| Overall Study | Study Specific Withdrawal Criteria | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 19 |
Baseline characteristics
| Characteristic | Anifrolumab 300 mg | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 6 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 175 Participants | 356 Participants | 181 Participants |
| Age, Continuous | 43.1 Years STANDARD_DEVIATION 11.95 | 42.1 Years STANDARD_DEVIATION 11.74 | 41.1 Years STANDARD_DEVIATION 11.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 54 Participants | 108 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 118 Participants | 238 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 16 Participants | 8 Participants |
| Geographic region Asia Pacific | 27 Participants | 53 Participants | 26 Participants |
| Geographic region Europe | 51 Participants | 97 Participants | 46 Participants |
| Geographic region Latin America | 35 Participants | 67 Participants | 32 Participants |
| Geographic region Rest of World (South Africa) | 3 Participants | 13 Participants | 10 Participants |
| Geographic region United States/Canada | 64 Participants | 132 Participants | 68 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 5 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 30 Participants | 60 Participants | 30 Participants |
| Race/Ethnicity, Customized Black or African American | 17 Participants | 42 Participants | 25 Participants |
| Race/Ethnicity, Customized Missing | 8 Participants | 16 Participants | 8 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 11 Participants | 22 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 110 Participants | 217 Participants | 107 Participants |
| Sex: Female, Male Female | 168 Participants | 338 Participants | 170 Participants |
| Sex: Female, Male Male | 12 Participants | 24 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 180 | 0 / 182 |
| other Total, other adverse events | 125 / 180 | 99 / 182 |
| serious Total, serious adverse events | 16 / 180 | 34 / 182 |
Outcome results
Primary
Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52
Composite endpoint BICLA was defined by meeting all of the following criteria: * Reduction of all baseline British Isles Lupus Assessment Group (BILAG)-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B * No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of \>0 points in SLEDAI-2K * No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment
Time frame: Baseline; Week 52
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 | 86 Participants |
| Placebo | Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 | 57 Participants |
p-value: 0.001395% CI: [6.3, 26.3]Cochran-Mantel-Haenszel
Secondary
Annualised Flare Rate Through 52 Weeks
A flare was defined as either 1 or more new British Isle Lupus Assessment Group (BILAG-2004) A or 2 or more new BILAG-2004 B items compared to the previous visit. The occurrence of a new flare was checked for each available visit versus the previous available visit up to Week 52. If no new flares occurred, the number of flares was set to 0. Otherwise all flares were counted leading to the maximum number of flares of 13. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25 (1 year). The flare exposure time is the time up to Week 52 (date of BILAG-2004 assessment at Week 52) or up to the date of last available BILAG-2004 assessment.
Time frame: Baseline to Week 52
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anifrolumab 300 mg | Annualised Flare Rate Through 52 Weeks | 0.43 Annualized flare rate ratio |
| Placebo | Annualised Flare Rate Through 52 Weeks | 0.64 Annualized flare rate ratio |
Comparison: Analysed using a negative binomial regression model. The response variable in the model is the number of flares over the 52-week treatment period. The model includes covariates of treatment group, and the stratification factors (SLEDAI-2K score at screening \[\<10 points vs \>=10 points\], Week 0 OCS dose \[\<10 mg/day vs \>=10 mg/day prednisone or equivalent\] and type I IFN gene signature test result at screening \[high vs low\]). The logarithm of the follow-up time is used as an offset variable.p-value: 0.080995% CI: [0.48, 0.94]Negative binomial regression
Secondary
Number of Participants Who Achieved and Maintained an Oral Corticosteroids (OCS) Dose of ≤7.5 mg/Day at Week 52 in the Sub-Group of Participants With Baseline OCS ≥10 mg/Day
Maintained OCS reduction was defined by meeting all of the following criteria: * Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 * Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment
Time frame: Week 40; Week 52
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug, who had a baseline OCS dose of ≥10 mg/day.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants Who Achieved and Maintained an Oral Corticosteroids (OCS) Dose of ≤7.5 mg/Day at Week 52 in the Sub-Group of Participants With Baseline OCS ≥10 mg/Day | 45 Participants |
| Placebo | Number of Participants Who Achieved and Maintained an Oral Corticosteroids (OCS) Dose of ≤7.5 mg/Day at Week 52 in the Sub-Group of Participants With Baseline OCS ≥10 mg/Day | 25 Participants |
Comparison: The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening \[\<10 points vs \>= 10 points\], Week 0 OCS dose \[\<10 mg/day vs \>=10 mg/day prednisone or equivalent\] and type I IFN gene signature test result at screening \[high vs low\]).p-value: 0.013595% CI: [6.8, 35.7]Cochran-Mantel-Haenszel
Secondary
Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 in the IFN Test-High Sub-group
Defined by meeting all of the following criteria: * Reduction of all baseline British Isles Lupus Assessment Group (BILAG)-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B * No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline to \>0 points in SLEDAI-2K * No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment
Time frame: Baseline; Week 52
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug, with a high interferon (IFN) test result at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 in the IFN Test-High Sub-group | 72 Participants |
| Placebo | Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 in the IFN Test-High Sub-group | 46 Participants |
Comparison: The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening \[\<10 points vs \>= 10 points\], Week 0 OCS dose \[\<10 mg/day vs \>=10 mg/day prednisone or equivalent\] and type I IFN gene signature test result at screening \[high vs low\]).p-value: 0.002295% CI: [6.5, 28.2]Cochran-Mantel-Haenszel
Secondary
Number of Participants With ≥50% Reduction in Joint Counts at Week 52 in The Sub-group of Participants With ≥6 Swollen and ≥6 Tender Joints at Baseline
50% reduction in the number of swollen and tender joints compared to baseline was defined by meeting all of the following criteria: * Achieve ≥50% reduction from baseline in the number of swollen and tender joints, separately * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment
Time frame: Baseline; Week 52
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug, and who had ≥6 swollen and ≥6 tender joints at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants With ≥50% Reduction in Joint Counts at Week 52 in The Sub-group of Participants With ≥6 Swollen and ≥6 Tender Joints at Baseline | 30 Participants |
| Placebo | Number of Participants With ≥50% Reduction in Joint Counts at Week 52 in The Sub-group of Participants With ≥6 Swollen and ≥6 Tender Joints at Baseline | 34 Participants |
Comparison: The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening \[\<10 points vs \>= 10 points\], Week 0 OCS dose \[\<10 mg/day vs \>=10 mg/day prednisone or equivalent\] and type I IFN gene signature test result at screening \[high vs low\]).p-value: 0.546995% CI: [-10.6, 20]Cochran-Mantel-Haenszel
Secondary
Number of Participants With a ≥50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12 in The Sub-Group of Participants With Baseline CLASI Activity Score of ≥10
50% reduction in CLASI activity score compared to baseline was defined by meeting all of the following criteria: * Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment
Time frame: Baseline; Week 12
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug, and who had a CLASI activity score of ≥10 at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants With a ≥50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12 in The Sub-Group of Participants With Baseline CLASI Activity Score of ≥10 | 24 Participants |
| Placebo | Number of Participants With a ≥50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12 in The Sub-Group of Participants With Baseline CLASI Activity Score of ≥10 | 10 Participants |
Comparison: The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening \[\<10 points vs \>= 10 points\], Week 0 OCS dose \[\<10 mg/day vs \>=10 mg/day prednisone or equivalent\] and type I IFN gene signature test result at screening \[high vs low\]).p-value: 0.039295% CI: [4.3, 43.6]Cochran-Mantel-Haenszel
Secondary
Number of Participants With a Potentially Clinically Important Change From Baseline in Clinical Laboratory Tests
Clinical laboratory tests were analyzed in a central clinical laboratory and included hematology, serum chemistry and urinalysis tests. Laboratory values were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE).
Time frame: Baseline to end of study (Maximum of 60 weeks)
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants With a Potentially Clinically Important Change From Baseline in Clinical Laboratory Tests | 72 Participants |
| Placebo | Number of Participants With a Potentially Clinically Important Change From Baseline in Clinical Laboratory Tests | 87 Participants |
Secondary
Number of Participants With a Potentially Clinically Important Change From Baseline in Vital Sign Measurements
Vital sign measurements included oral temperature, blood pressure (BP), pulse rate, and respiratory rate. Vital signs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE).
Time frame: Baseline to end of study (Maximum of 60 weeks)
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants With a Potentially Clinically Important Change From Baseline in Vital Sign Measurements | 45 Participants |
| Placebo | Number of Participants With a Potentially Clinically Important Change From Baseline in Vital Sign Measurements | 45 Participants |
Secondary
Number of Participants With One or More Adverse Events (AEs)
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE). The reported value is inclusive of serious and non-serious AEs.
Time frame: Baseline to end of study (Maximum of 60 weeks)
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants With One or More Adverse Events (AEs) | 162 Participants |
| Placebo | Number of Participants With One or More Adverse Events (AEs) | 154 Participants |
Secondary
Number of Participants With One or More Adverse Events of Special Interest (AESIs)
An AESI is an adverse event (AE) of scientific and medical concern specific to understanding biologics. An AESI may be serious or non-serious. AESI are serious infections, including non-opportunistic serious infections, opportunistic infections, anaphylaxis, malignancy, herpes zoster, tuberculosis (TB) (including latent TB), influenza, vasculitis (non-systemic lupus erythematosus \[SLE\]), and major adverse cardiovascular events (MACE) (including stroke, myocardial infarction \[MI\], or cardiovascular death). AESIs were collected throughout the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE).
Time frame: Baseline to end of study (Maximum of 60 weeks)
Population: Full Analysis Set: All participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anifrolumab 300 mg | Number of Participants With One or More Adverse Events of Special Interest (AESIs) | 29 Participants |
| Placebo | Number of Participants With One or More Adverse Events of Special Interest (AESIs) | 20 Participants |